Healthy Skepticism Library item: 1081

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Publication type: news

Pollack A.
Talking Up a Drug for This (and That)
The New York Times 2003 Apr 27
http://www.nytimes.com/2003/04/27/business/talking-up-a-drug-for-this-and-that.html?scp=9&sq=

Full text:

THE drug Actimmune would not appear to have great sales potential. It is
approved to treat only two rare diseases that together afflict just 800
Americans.
Yet sales nearly tripled last year, to $106 million, and its
manufacturer expects them to exceed $160 million this year. Virtually
all those sales are for an unapproved use: to treat idiopathic pulmonary
fibrosis, a scarring of the lungs that afflicts 50,000 to 75,000
Americans and is often fatal.
The sales have stirred controversy about the drug and its maker, a small
company called InterMune. Some doctors and patients hail the drug
because most patients have no other treatments available and face death
from the disease. Critics, however, say the company has been overselling
an unproven remedy at a cost to each patient of about $50,000 a year,
for injections three times a week.
“We’ve had patients who have been desperate enough to question
mortgaging their house or giving up their life savings to get this
treatment,” said Dr. Jonathan B. Orens, medical director for lung
transplants at Johns Hopkins Hospital in Baltimore. “It’s our
responsibility, ethically, to make sure patients aren’t given treatments
and false hopes that cost a lot of money.”
A clinical trial completed last year suggested that Actimmune can
prolong the lives of some patients with pulmonary fibrosis. But the
company concedes that the results of the trial were not strong enough
for the drug to be approved to treat that disease. Still, when the
trial’s results were announced, the company predicted that sales of
Actimmune would reach $400 million to $500 million a year, even without
approval.
The company has also been the subject of debate among investors, and so
far, the doubters have been winning. InterMune’s stock has lost half its
value since October, closing on Friday at $18.62.
Actimmune’s sales represent an extreme case of what is known as
off-label use. Doctors are allowed to prescribe a drug for unapproved
uses, but drug companies cannot promote such uses, though in some cases
they can provide educational material to doctors.
But drawing the line is tricky, and regulations are in flux. The Food
and Drug Administration says restrictions on off-label marketing may
conflict with the right to free speech, and it is considering relaxing
the rules.
Some other drugs are sold mainly for nonapproved uses. Provigil, a drug
from Cephalon that increases alertness, is approved only for narcolepsy,
but most of its nearly $200 million in sales last year were for
sleepiness linked to other conditions. More than 90 percent of the $119
million in sales of thalidomide, from Celgene, were for cancer, not for
its approved use, leprosy. Most of the $2.3 billion in sales of
Neurontin, from Pfizer, are for uses other than epilepsy, for which it
is approved.

THROUGH off-label use, doctors can start treatment without waiting years
for a new approval. Patients, particularly those with life-threatening
diseases, often clamor for such drugs. But critics say the system allows
companies to circumvent scientifically valid but costly trials.
Cephalon and Celgene have received reprimands from the F.D.A., and
Pfizer has been sued over the issue. InterMune has never been warned by
the F.D.A.; the company’s backers say this shows that it is playing by
the rules. Executives of the company say it is only responding to
demand.
“We don’t market it” for pulmonary fibrosis, said W. Scott Harkonen,
InterMune’s chief executive, in an interview. “There’s been a lot of
interest in the medical community, and we’ve responded to those
requests.”
But there is evidence that the company has actively stirred interest. At
an investors’ conference in September, it said its sales force included
60 pulmonary specialists to call on every lung doctor in the country – “all in the context of our education and awareness program,” a company
executive said. Its annual report for 2002 said profits on Actimmune
were low because of royalties and “direct costs of marketing.”
InterMune has sponsored dinners at which doctors hear speeches by
pulmonary fibrosis experts, who mention Actimmune. It has set up booths
at pulmonology medical meetings. It financed the creation of a nonprofit
patient advocacy group called the Coalition for Pulmonary Fibrosis.
“They are using the education loophole in a way that becomes advertising
and promotion,” said Michael Rosenzweig, president of the Pulmonary
Fibrosis Foundation, an advocacy group based in Chicago.
The company has also set up a hot line for doctors and patients to order
the drug, and it helps them win reimbursement from many insurers.
“We have almost always been successful” in having patients reimbursed,
said Dr. Talmadge E. King Jr., chief of medicine at San Francisco
General Hospital. “Most of the time we have just sent them to
InterMune.”
Dr. Harkonen said that InterMune had no control over the content of the
dinner speeches and that the other activities were expected by doctors
and patients. “We are committed to being leaders in the development of
new therapies,” he said. “To do that, we need a presence in the medical
communities.”
InterMune’s supporters say its activities help patients and raise
awareness of a disease that is hard to diagnose. If that indirectly
helps the company, they add, so be it. The supporters include many
leading pulmonary fibrosis experts who are advisers to InterMune.
“The company, in my opinion, has done a tremendous service for the
disease,” said Dr. Paul W. Noble, an associate professor of medicine at
Yale who has given speeches sponsored by InterMune.
Dr. King of San Francisco General, who is also a professor at the
University of California at San Francisco and an adviser to InterMune,
said, “I’ve always had the feeling the company put the right information
out there.” Actimmune is “not a miracle drug, but it does appear to
prolong life in a subset of patients.”
One pulmonary fibrosis patient, Alan Raff, 74, of Coral Gables, Fla.,
says the drug has halted the progression of his disease for three years.
Speaking of InterMune’s activities, he said, “I don’t know what’s not to
like, because in some cases it’s saving lives.”
Patients with idiopathic pulmonary fibrosis face a grim death, usually
two to five years after diagnosis. The scarring of the lungs makes it
harder and harder for them to breathe, until they essentially suffocate.
The only proven treatment is a lung transplant, but donated lungs are
scarce. Steroids are often used – also off label – but many doctors say
they do not work and have side effects. The comedian Jerry Lewis, who
has pulmonary fibrosis, has become bloated from the steroids.
InterMune, based in Brisbane, Calif., south of San Francisco, is one of
a new breed of companies that do not invent drugs but instead license
neglected drugs from bigger companies. Though the company has two other
drugs on the market, Actimmune accounts for the vast bulk of its sales.
Actimmune is a protein called gamma interferon developed by Genentech,
the biotechnology pioneer, which licensed it to Connetics, a small drug
company. Dr. Harkonen, who worked at Connetics, persuaded it to license
the drug to InterMune, which he formed in 1998.
Though InterMune initially envisioned using the drug to treat infectious
disease or cancer, its plans changed in 1999, when a paper published in
The New England Journal of Medicine reported striking results from a
small trial for pulmonary fibrosis. The trial had only 18 patients, but
the 9 who received the drug all had improved lung function, while those
in the control group worsened.

SO InterMune organized a big trial, winning praise from doctors and
patients. It also began to sell the drug based on the small trial.
The company also started the Coalition for Pulmonary Fibrosis, the
advocacy group. As first reported by TheStreet.com, the executive
director, Mark Shreve, worked for Edelman Public Relations, which
represented InterMune, and the coalition at first was based in Edelman’s
San Francisco office. The Internal Revenue Service filing for 2001 from
the coalition reports only one donation – $187,000 from InterMune – with
$170,000 of it being paid to Edelman.
In an interview, Mr. Shreve said that he had quit Edelman and now ran
the coalition from his home near Scottsdale, Ariz. He said that there
were now many other donors.
The coalition’s chairman, Dr. Marvin Schwarz of the University of
Colorado, also an InterMune adviser, said the group was not a marketing
front. “The coalition has never made a statement about the drug that I’m
aware of,” he said.
The big trial, involving 330 patients, ended last year and was intended
to see whether the drug improved lung function. But the lungs of those
who took Actimmune were not significantly better than the lungs of
patients who received a placebo.
Somewhat unexpectedly, however, patients who took Actimmune often lived
longer. That result was not statistically significant over all. But in a
subset of patients with milder disease, there was a large and
statistically significant difference: only six who got the drug died,
compared with 21 who got a placebo.
The company trumpeted the results in a news release in August. The stock
soared, nearly doubling by the end of October.
A committee of independent doctors who had monitored the trial to assure
patient safety quickly accused the company of exaggerating the drug’s
benefits while playing down side effects, like a greater incidence of
nonfatal pneumonia, doctors involved in the trial say.
Dr. Thomas R. Fleming, a biostatistician at the University of Washington
and the chairman of the committee, said that he was bound by a
confidentiality agreement. But he said, “I do think the subsequent
reports the company has given do provide a much more detailed
perspective of what was learned at the trial.”
The results have led to a quandary for doctors and patients. Some
doctors say it is dangerous to jump to conclusions about survival
because the trial was not designed to measure that. Skeptics also wonder
how the drug could prolong life if it did not improve lung function.
“It’s not clear what to make of the mortality data,” said Dr. Fernando
J. Martinez of the University of Michigan, an adviser to InterMune. He
said he suspected that the drug did have some effect, but he has
concerns that company marketing officials continue to provide snippets
of data before complete results have been published.
Still, some doctors say the hint of a survival benefit is too strong to
ignore. “We’re talking about a population that has no shot,” said Dr.
Richard Miller, chief of pulmonology at St. Michael’s Medical Center in
Newark. “Something is better than nothing.”
InterMune has said that 3,000 patients were being treated with Actimmune
at the end of 2002, up from 2,500 three months earlier.
Some doctors say that even if the drug does not work, it is worth trying
because it is generally safe. But French doctors reported recently that
four patients who took the drug had deteriorated rapidly and died. Those
patients, however, were far sicker than the ones in InterMune’s trial.
Karen Burnard of Finesville, N.J., said she thought Actimmune had
contributed to the death in March of her brother, Jack Dwyer, a
64-year-old middle-school teacher who lived in Alloway, N.J.
Actimmune made him sick and unable to eat, Ms. Burnard said. “Food
tasted like metal, and by the end he had lost 57 pounds,” she said. He
stopped taking the drug, she said, but by then was too sick to qualify
for a lung transplant.
Recent developments have dimmed Wall Street’s view of the company’s
prospects. In January, InterMune announced that the survival benefit
conferred by the drug on patients with milder disease had diminished
somewhat when they were followed for three to five additional months,
though the difference was still statistically significant.
At the end of January, David A. Cory, the senior vice president for
sales and marketing, left InterMune, the company said, to “pursue other
opportunities.” On March 31, the company said in its annual report that
it no longer believed that Actimmune could achieve $400 million to $500
million in annual sales based on the clinical trial results.
Moreover, competition is developing. Among the drugs expected to be
tested are Tracleer, sold by Actelion of Switzerland for pulmonary
hypertension; Gleevec, the promising cancer drug from Novartis; and
Enbrel, the big-selling arthritis treatment from Amgen.
InterMune has said that it is planning another trial, so it will be at
least three years before it can seek F.D.A. approval for Actimmune’s use
in pulmonary fibrosis.
Investors will be closely watching InterMune’s first-quarter results, to
be announced on Tuesday, and presentations at the American Thoracic
Society meeting in mid-May. In a news release, the company has promised
that exciting data will be announced there that may explain how
Actimmune works. That may persuade the doubters and promote its use. But
the debate among doctors and patients and on Wall Street is likely to
continue.